Low-intensity Ultrasound Improves Cognitive Function in Patients with Alzheimer’s Disease

Abstract

Objective To investigate that the utilization of low-intensity ultrasound for Alzheimer’s continuum with mild cognitive impairment or early-stage dementia will result in positive cognitive effects through ultrasound neuromodulation.

Methods All participants had positive findings on the 18F-florbetaben amyloid PET image prior to ultrasound treatment. To ensure the safety of ultrasound treatment, Brain MRI was conducted before and after treatment. We used low intensity ultrasound device consisting of 4 individual transducers with fundamental frequency of 250kHz. The sonication was administered three times a week for a total duration of four weeks. Each session consisted of a 30-minute sonication duration.

Results Quantitative analysis showed that the time of Trail Making Test-Black and White (TMT-BW) after four weeks of ultrasound treatment were less than baseline (TMT-BW A, 115.6±70.1 vs. 87.3±56.2, P=0.017; TMT-BW B, 316.2±160.6 vs. 231.3±64.3, P=0.044). We compared nodal degree values through functional connectivity analysis between the pre and post-treatment. We observed moderately higher degrees in the parietal (P=0.070) and temporal lobes (P=0.089), as well as the whole brain (P=0.085) after the treatment, suggesting an integration of functional brain organization. We found larger changes in the earlyonset group, indicating that the treatment may be more efficient for groups more vulnerable to the disease. Comparing FDG PET results between pre and post-treatment, we observed a greater increase in FDG PET uptake in the frontal and parietal regions in the early-onset group compared to the late-onset group. Post-ultrasound treatment Brain MRI did not reveal any evidence of cerebral microbleeds or edema.

Conclusion Our study confirms the safety of low-intensity ultrasound therapy in patients with early-stage AD. Furthermore, it demonstrates that ultrasound therapy can lead to clinical improvements in the AD continuum.